tbuckley/cabot-search huggingface dataset:
Cholesterol 24-hydroxylase at the choroid plexus contributes to brain immune homeostasis
Authors: Afroditi Tsitsou-Kampeli, Stefano Suzzi, Mor Kenigsbuch, Akisawa Satomi, Romano Strobelt, Oded Singer, Ester Feldmesser, Maitreyee Purnapatre, Sarah Phoebeluc Colaiuta, Eyal David, Liora Cahalon, Oliver Hahn, Tony Wyss-Coray, Yosef Shaul, Ido Amit, Michal Schwartz
Journal: Cell Reports Medicine (2023)

<h2>Summary</h2> The choroid plexus (CP) plays a key role in remotely controlling brain function in health, aging, and disease. Here, we report that CP epithelial cells express the brain-specific cholesterol 24-hydroxylase (CYP46A1) and that its levels are decreased under different mouse and human brain conditions, including amyloidosis, aging, and SARS-CoV-2 infection. Using primary mouse CP cell cultures, we demonstrate that the enzymatic product of CYP46A1, 24(<i>S</i>)-hydroxycholesterol, downregulates inflammatory transcriptomic signatures within the CP, found here to be elevated across multiple neurological conditions. <i>In vitro</i>, the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) downregulates CYP46A1 expression, while overexpression of CYP46A1 or its pharmacological activation in mouse CP organ cultures increases resilience to TNF-α. <i>In vivo</i>, overexpression of CYP46A1 in the CP in transgenic mice with amyloidosis is associated with better cognitive performance and decreased brain inflammation. Our findings suggest that CYP46A1 expression in the CP impacts the role of this niche as a guardian of brain immune homeostasis.
Cover Image, Volume 43, Issue 11
Authors: Yongzhan Nie, Xianchun Gao, Xiqiang Cai, Zhen Wu, Qiaoyi Liang, Guobing Xu, Na Liu, Peng Gao, Jingyu Deng, Hongzhi Xu, Zhanlong Shen, Changqi Cao, Fenrong Chen, Nannan Zhang, Yongxi Song, Mingjun Sun, Chengyin Liu, Guangpeng Zhou, Weili Han, Jianhua Dou, Huahong Xie, Liping Yao, Zhiguo Liu, Gang Ji, Xin Wang, Qingchuan Zhao, Lei Shang, Daiming Fan, Xiaoliang Han, Jianlin Ren, Han Liang, Zhenning Wang, Jinhai Wang, Qi Wu, Jun Yu, Kaichun Wu
Journal: Cancer Communications (2023)

The cover image is based on the Correspondence Combining methylated SEPTIN9 and RNF180 plasma markers for diagnosis and early detection of gastric cancer by Yongzhan Nie et al., https://doi.org/10.1002/cac2.12478.
Mendelian Randomization as a Tool for Cardiovascular Research
Authors: Michael G. Levin, Stephen Burgess
Journal: JAMA Cardiology (2023)

Mendelian randomization (MR) is a statistical approach that has become increasingly popular in the field of cardiovascular disease research. It offers a way to infer potentially causal relationships between risk factors and outcomes using observational data, which is particularly important in cases where randomized clinical trials are not feasible or ethical. With the growing availability of large genetic data sets, MR has become a powerful and accessible tool for studying the risk factors for cardiovascular disease.
A neural substrate for short-term taste memories
Authors: Zhang Juen, Miguel Villavicencio, Charles S. Zuker
Journal: Neuron (2023)

Real-time decisions on what foods to select for consumption, particularly in the wild, require a sensitive sense of taste and an effective system to maintain short-term taste memories, also defined as working memory in the scale of seconds. Here, we used a behavioral memory assay, combined with recordings of neural activity, to identify the brain substrate for short-term taste memories. We demonstrate that persistent activity in taste cortex functions as an essential memory trace of a recent taste experience. Next, we manipulated the decay of this persistent activity and showed that early termination of the memory trace abolished the memory. Notably, extending the memory trace by transiently disinhibiting taste cortical activity dramatically extended the retention of a short-term taste memory. Together, our results uncover taste cortex as a neural substrate for working memory and substantiate the role of sensory cortex in memory-guided actions while imposing meaning to a sensory stimulus.
Mendelian Randomization and Cardiovascular Disease—Enabling Expert Readership
Authors: Pradeep Natarajan, Clyde W. Yancy
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Error in Author Name
Journal: JAMA Cardiology (2023)

Ramsey M. Wehbe, MD, MSAI; Aggelos K. Katsaggelos, PhD; Kristian J. Hammond, PhD; Ha Hong, PhD; Faraz S. Ahmad, MD, MS; David Ouyang, MD; Sanjiv J. Shah, MD; Patrick M. McCarthy, MD; James D. Thomas, MD
Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer
Authors: Kelly Boelaars, Laura Goossens-Kruijssen, Di Wang, Charlotte M de Winde, Ernesto Rodriguez, Dimitri Lindijer, Babet Springer, Irene van der Haar Àvila, Aram de Haas, Laetitia Wehry, Louis Boon, Reina E Mebius, Nadine van Montfoort, Manfred Wuhrer, Joke M M den Haan, Sandra J van Vliet, Yvette van Kooyk
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T cells are located distant from the tumor islands (immune excluded). Converting the TME to an immune-inflamed state, allowing T-cell infiltration, could increase the success of immunotherapy in PDAC. Method In this study, we use the KPC3 subcutaneous PDAC mouse model to investigate the role of tumor-derived sialic acids in shaping the tumor immune landscape. A sialic acid deficient KPC3 line was generated by genetic knock-out of the CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) enzyme, a critical enzyme in the synthesis of sialic acid-containing glycans. The effect of sialic acid-deficiency on immunotherapy efficacy was assessed by treatment with anti-programmed cell death protein 1 (PD-1) and agonistic CD40. Result The absence of sialic acids in KPC3 tumors resulted in increased numbers of CD4 + and CD8 + T cells in the TME, and reduced frequencies of CD4 + regulatory T cells (Tregs) within the T-cell population. Importantly, CD8 + T cells were able to infiltrate the tumor islands in sialic acid-deficient tumors. These favorable alterations in the immune landscape sensitized sialic acid-deficient tumors to immunotherapy, which was ineffective in sialic acid-expressing KPC3 tumors. In addition, high expression of sialylation-related genes in human pancreatic cancer correlated with decreased CD8 + T-cell infiltration, increased presence of Tregs, and poorer survival probability. Conclusion Our results demonstrate that tumor-derived sialic acids mediate T-cell exclusion within the PDAC TME, thereby impairing immunotherapy efficacy. Targeting sialic acids represents a potential strategy to enhance T-cell infiltration and improve immunotherapy outcomes in PDAC.
rtPA-loaded fucoidan polymer microbubbles for the targeted treatment of stroke
Authors: Louise Fournier, Myriam Abioui-Mourgues, Georges Chabouh, Rachida Aid, Thibault De La Taille, Olivier Couture, Denis Vivien, Cyrille Orset, Cédric Chauvierre
Journal: Biomaterials (2023)

Systemic injection of thrombolytic drugs is the gold standard treatment for non-invasive blood clot resolution. The most serious risks associated with the intravenous injection of tissue plasminogen activator-like proteins are the bleeding complication and the dose related neurotoxicity. Indeed, the drug has to be injected in high concentrations due to its short half-life, the presence of its natural blood inhibitor (PAI-1) and the fast hepatic clearance (0.9 mg/kg in humans, 10 mg/kg in mouse models). Overall, there is a serious need for a dose-reduced targeted treatment to overcome these issues. We present in this article a new acoustic cavitation-based method for polymer MBs synthesis, three times faster than current hydrodynamic-cavitation method. The generated MBs are ultrasound responsive, stable and biocompatible. Their functionalization enabled the efficient and targeted treatment of stroke, without side effects. The stabilizing shell of the MBs is composed of Poly-Isobutyl Cyanoacrylate (PIBCA), copolymerized with fucoidan. Widely studied for its targeting properties, fucoidan exhibit a nanomolar affinity for activated endothelium and activated platelets (P-selectins). Secondly, the thrombolytic agent (rtPA) was loaded onto microbubbles (MBs) with a simple adsorption protocol. Hence, the present study validated the in vivo efficiency of rtPA-loaded Fuco MBs to be over 50 % more efficient than regular free rtPA injection for stroke resolution. In addition, the relative injected rtPA grafted onto targeting MBs was 1/10th of the standard effective dose (1 mg/kg in mouse). As a result, no hemorrhagic event, BBB leakage nor unexpected tissue distribution were observed.
Perspectives and Strategies to Minimize Harm From Melanoma Diagnosis
Authors: Klaus J. Busam, Pedram Gerami, Richard A. Scolyer
Journal: JAMA Dermatology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Survey: Which Children Visit ED for Mental Health Concerns, and Why
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Relationship between air quality and asthma-related emergency hospital admissions in Mexico City 2017–2019
Authors: Louise Hayes, Juan Manuel Mejia-Arangure, Adam Errington, Lindsay Bramwell, Elizabeth Vega, Juan Carlos Nunez-Enriquez, Anil Namdeo, Jane Entwistle, Yosune Miquelajauregui, Mónica Jaimes-Palomera, Nancy Torres, R Alberto Rascón-Pacheco, David A Duarte-Rodríguez, Richard McNally
Journal: Thorax (2023)

Background Previous studies found exposure to air pollution leads to exacerbations of asthma in paediatric and adult patients and increases asthma-related emergency hospital admissions (AREHA). Methods AREHAs and levels of air pollutants (PM 10 , PM 2.5 and NO 2 ) were obtained from Mexico City for the period 2017–2019. A time-series approach was used to explore the relationship between air pollutants and AREHA. Relative risks of AREHA were estimated using a negative binomial regression in young children (less than 5 years) and adults (greater than 18 years). Results There was a positive association between AREHA and PM 10 , PM 2.5 and NO 2 in adults, which remained after mutual adjustment for these pollutants. The relative risk (RR) of admission in adults increased by 3% (95% CI 1% to 4%) for a 10 µg/m 3 increase in PM 10 , 1% (0.03% to 3%) for a 5 µg/m 3 increase in PM 2.5 and by 1% (0.06% to 2%) for a 5 µg/m 3 increase in NO 2 . In contrast, in young children, AREHAs were negatively associated with PM 10 after adjustment for NO 2 (RR 0.97 (0.95 to 0.99) for a 10 µg/m 3 and with NO 2 after adjustment for PM 10 and PM 2.5 (RR 0.98 (0.96 to 0.99) and 0.97 (0.96 to 0.99), respectively, for a 5 µg/m 3 increase in NO 2 ). AREHAs in children were not associated with PM 2.5 after adjustment for NO 2 . Conclusions Ambient air pollution, within the previous week, was associated with emergency hospital admissions for asthma to public hospitals in adults in Mexico City. The relationship in children was less consistent. Further work is needed to explore why differences between adults and children exist to inform appropriate interventions to benefit public health.
Cartilage-on-a-chip with magneto-mechanical transformation for osteoarthritis recruitment
Authors: Hao Liu, Xiangyi Wu, Rui Liu, Weijun Wang, Dagan Zhang, Qing Jiang
Journal: Bioactive Materials (2023)

Osteoarthritis (OA) is a prevalent joint disease primarily induced by overstrain, leading to disability and significantly impacting patients' quality of life. However, current OA studies lack an ideal in vitro model, which can recapitulate the high peripheral strain of the joint and precisely model the disease onset process. In this paper, we propose a novel cartilage-on-a-chip platform that incorporates a biohybrid hydrogel comprising Neodymium (NdFeB)/Poly-GelMA-HAMA remote magneto-control hydrogel film. This platform facilitates chondrocyte culture and stress loading, enabling the investigation of chondrocytes under various stress stimuli. The Neodymium (NdFeB)/Poly-GelMA-HAMA hydrogel film exhibits magneto-responsive shape-transition behavior, further dragging the chondrocytes cultured in hydrogels under magnetic stimulation. It was investigated that inflammation-related genes and proteins in chondrocytes are changed with mechanical stress stimulation in the cartilage-on-a-chip. Especially, MMP-13 and the proportion of collagen secretion are upregulated, showing a phenotype similar to that of real human osteoarthritis. Therefore, we believed that this cartilage-on-a-chip platform provides a desired in vitro model for osteoarthritis, which is of great significance in disease research and drug development.
Integrating Fluorescence and Magnetic Resonance Imaging in Biocompatible Scaffold for Real‐Time Bone Repair Monitoring and Assessment
Authors: Ai Yang, Yue Wang, Qian Feng, Kanwal Fatima, Qianqian Zhang, Xiaojun Zhou, Chuanglong He
Journal: Advanced Healthcare Materials (2023)

Abstract In situ monitoring of bone tissue regeneration progression is critical for the development of bone tissue engineering scaffold. However, engineered scaffolds that can stimulate osteogenic progress and allow for non‐invasive monitoring of in vivo bone regeneration simultaneously are rarely reported. Based on a hard‐and‐soft integration strategy, a multifunctional scaffold composed of 3D printed microfilaments and a hydrogel network containing simvastatin (SV), indocyanine green‐loaded superamphiphiles, and aminated ultrasmall superparamagnetic iron oxide nanoparticles (USPIO‐NH 2 ) is fabricated. Both in vitro and in vivo results demonstrate that the as‐prepared scaffold significantly promotes osteogenesis through controlled SV release. The biocomposite scaffold exhibits alkaline phosphatase‐responsive near‐infrared II fluorescence imaging. Meanwhile, USPIO‐NH 2 within the co‐crosslinked nanocomposite network enables the visualization of scaffold degradation by magnetic resonance imaging. Therefore, the biocomposite scaffold enables or facilitates non‐invasive in situ monitoring of neo‐bone formation and scaffold degradation processes following osteogenic stimulation, offering a promising strategy to develop theranostic scaffolds for tissue engineering.
Peptide-based approaches to directly target alpha-synuclein in Parkinson’s disease
Authors: Scott G. Allen, Richard M. Meade, Lucy L. White Stenner, Jody M. Mason
Journal: Molecular Neurodegeneration (2023)

Abstract Peptides and their mimetics are increasingly recognised as drug-like molecules, particularly for intracellular protein-protein interactions too large for inhibition by small molecules, and inaccessible to larger biologics. In the past two decades, evidence associating the misfolding and aggregation of alpha-synuclein strongly implicates this protein in disease onset and progression of Parkinson’s disease and related synucleinopathies. The subsequent formation of toxic, intracellular, Lewy body deposits, in which alpha-synuclein is a major component, is a key diagnostic hallmark of the disease. To reach their therapeutic site of action, peptides must both cross the blood-brain barrier and enter dopaminergic neurons to prevent the formation of these intracellular inclusions. In this review, we describe and summarise the current efforts made in the development of peptides and their mimetics to directly engage with alpha-synuclein with the intention of modulating aggregation, and importantly, toxicity. This is a rapidly expanding field with great socioeconomic impact; these molecules harbour significant promise as therapeutics, or as early biomarkers during prodromal disease stages, or both. As these are age-dependent conditions, an increasing global life expectancy means disease prevalence is rising. No current treatments exist to either prevent or slow disease progression. It is therefore crucial that drugs are developed for these conditions before health care and social care capacities become overrun.
Indications and surgical technique for distraction osteogenesis of the alveolar bone for augmentation prior to insertion of dental implants
Authors: Hans‐Joachim Nickenig, Joachim E. Zöller, Matthias Kreppel
Journal: Periodontology 2000 (2023)

Abstract When bone is limited, short, ultra‐short, or narrow implants help to restore oral rehabilitation with an acceptable long‐term outcome. This becomes more difficult with severe vertical bone loss. Guided bone regeneration, onlay block transplantation, or sandwich osteotomy have been established to build up these defects. The alternative to the alveolar distraction osteogenesis (ADO) has only been established in some centers, with a standardized protocol. On the one hand, ADO is a biological procedure that allows almost a “restitutio ad integrum” when building up hard and soft tissue. On the other hand, there are clear indications, limitations, and complications of the procedure in the literature. In addition to the literature, concept of Tissue Regeneration by Alveolar Callusdistraction Cologne (TRACC), which has been practiced successfully for over two decades, will be presented for different indications.
Clinical presentation, shock severity and mortality in patients with de novo versus acute‐on‐chronic heart failure‐related cardiogenic shock
Authors: Jonas Sundermeyer, Caroline Kellner, Benedikt N. Beer, Lisa Besch, Angela Dettling, Letizia Fausta Bertoldi, Stefan Blankenberg, Jeroen Dauw, Zouhir Dindane, Dennis Eckner, Ingo Eitel, Tobias Graf, Patrick Horn, Joanna Jozwiak‐Nozdrzykowska, Paulus Kirchhof, Stefan Kluge, Axel Linke, Ulf Landmesser, Peter Luedike, Enzo Lüsebrink, Nicolas Majunke, Norman Mangner, Octavian Maniuc, Sven Möbius Winkler, Peter Nordbeck, Martin Orban, Federico Pappalardo, Matthias Pauschinger, Michal Pazdernik, Alastair Proudfoot, Matthew Kelham, Tienush Rassaf, Hermann Reichenspurner, Clemens Scherer, Paul Christian Schulze, Robert H.G. Schwinger, Carsten Skurk, Marek Sramko, Guido Tavazzi, Holger Thiele, Luca Villanova, Nuccia Morici, Ephraim B. Winzer, Dirk Westermann, Finn Gustafsson, Benedikt Schrage
Journal: European Journal of Heart Failure (2023)

Aims Heart failure‐related cardiogenic shock (HF‐CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute‐on‐chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute‐on‐chronic HF‐CS. Methods and results In this international observational study, patients with HF‐CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30‐day mortality, adjusted logistic/Cox regression models were fitted. Patients ( n = 1030) with HF‐CS were analysed, of whom 486 (47.2%) presented with de novo HF‐CS and 544 (52.8%) with acute‐on‐chronic HF‐CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute‐on‐chronic HF‐CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute‐on‐chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10–1.72, p = 0.005). Conclusion In this large HF‐CS cohort, acute‐on‐chronic HF‐CS was associated with more severe CS and higher mortality risk compared to de novo HF‐CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF‐CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.